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Dangerous R loops form in the absence of H3K9 methylation

Nature Genetics volume 48, pages 1299–1300 (2016)Cite this article

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Methylation of histone H3 on lysine 9 (H3K9) is a hallmark of transcriptionally inactive heterochromatin that is deregulated in pathological conditions. A new study shows that complete loss of H3K9 methylation in Caenorhabditis elegans leads to derepression of repetitive elements and formation of DNA:RNA hybrids (R loops), resulting in increased rates of repeat-specific mutation.

Methylated forms of H3K9 are enriched in silent heterochromatic regions such as telomeres, pericentric heterochromatin and repetitive elements. Changes in heterochromatin have been observed during cellular differentiation and in cancer cells1,2, and increased H3K9 methylation has been associated with cancer initiation and progression, and with poor prognosis. In mammals, several lysine methyltransferases (KMTs) can transfer the methyl groups on H3K9 (where the lysine can be mono-, di- or trimethylated), and loss of these enzymes has profound consequences, including early embryonic lethality, as observed in mice lacking Setdb1, Ehmt2 (G9a), and Suv39h1 together with Suv39h2 (refs. 3,4,5). The redundant functions of the H3K9 KMTs and the gravity of their mutant phenotypes make it difficult to study the impact that complete loss of H3K9 methylation would have on the animal. Taking advantage of the fact that C. elegans express only two H3K9-specific KMTs (set-25 and met-2) and that worms lacking both proteins are viable6, Susan Gasser and colleagues report in this issue7 on the biological function of H3K9 methylation and the consequences of its loss.

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Figure 1: H3K9 methylation regulates genome stability.

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  1. Anna Elisabetta Salcini is at the Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.,

    Anna Elisabetta Salcini

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  1. Anna Elisabetta Salcini
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Correspondence to Anna Elisabetta Salcini.

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Salcini, A. Dangerous R loops form in the absence of H3K9 methylation. Nat Genet 48, 1299–1300 (2016). https://doi.org/10.1038/ng.3705

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